Method and immunoabsorbents for specific detection and absorption of antibodies associated with celiac disease and dermatitis herpetiformis

Abstract

The present invention relates to fusion peptides that are derived from components of gliadin, to a method and reagents for the serological diagnosis of celiac disease or dermatitis herpetiformis by way of assaying antibodies that are directed against modified gliadin. The invention also relates to methods and pharmaceutical compositions for treating said diseases by specific immunoabsorption of these antibodies.

The invention claimed is: 
     
       1. A polypeptide comprising one or more of a first peptide sequence and one or more of a second peptide sequence wherein the first peptide sequence is SEQ ID NO:2 and the second peptide sequence is SEQ ID NO:3, wherein SEQ ID NO:2 and SEQ ID NO:3 partially overlap, and wherein the binding of the polypeptide to antibodies specific for celiac disease and dermatitis herpetiformis is comparable to the binding of the polypeptide according to SEQ ID NO:7 to the antibodies specific for celiac disease and dermatitis herpetiformis. 
     
     
       2. The polypeptide according to  claim 1 , wherein the polypeptide comprises one or more polypeptides consisting of at least 10, at least 14, at least 15, or at least 16 successive amino acids of SEQ ID NO:4 or wherein the polypeptide comprises one or more polypeptides according to SEQ ID NO:4. 
     
     
       3. The polypeptide according to  claim 1 , comprising three polypeptides according to SEQ ID NO:4. 
     
     
       4. The polypeptide according to  claim 1 , comprising one or several polypeptide sequences according to SEQ ID NO:7. 
     
     
       5. A polymer comprising 2 to 20 polypeptides of  claim 1  joined together. 
     
     
       6. The polypeptide according to  claim 1 , wherein the polypeptide is produced recombinantly or with common biochemical means of polypeptide synthesis. 
     
     
       7. The polypeptide according to  claim 1 , wherein the polypeptide is bound to a reporter molecule or to a solid phase. 
     
     
       8. A method for the diagnosis of celiac disease or dermatitis herpetiformis, comprising:
 contacting a liquid biological sample from a patient with one or several polypeptides under conditions that the binding of antibodies from the biological sample to said polypeptides can take place, wherein the polypeptide comprises one or more of a first peptide sequence and one or more of a second peptide sequence, and wherein (1) the first peptide sequence is SEQ ID NO:2 or a sequence comprising up to 30% of amino acid of SEQ ID NO:2 deleted or substituted by conservative amino acid substitutions, (2) the second peptide sequence is SEQ ID NO:3 or a sequence comprising up to 30% of amino acid sequence of SEQ ID NO:3 deleted or substituted by conservative amino acid substitutions, and (3) the binding of the polypeptide to antibodies specific for celiac disease and dermatitis herpetiformis is comparable to the binding of the polypeptide according to SEQ ID NO:7 to the antibodies specific for celiac disease and dermatitis herpetiformis, and 
 detecting the presence or absence of the antibodies that bind to one of the polypeptides, whereby diagnosing celiac disease or dermatitis herpetiformis. 
 
     
     
       9. The method according to  claim 8 , wherein the liquid biological sample from a patient is contacted with at least two different polypeptides. 
     
     
       10. The method according to  claim 8 , wherein the binding of the antibodies to the fusion polypeptides is detected using an immunofluorescence test, microarray, ELISA, luminescence test, blot, radioimmunoassay, Western blot or dot blot. 
     
     
       11. A test kit for the detection of antibodies, comprising a polypeptide that comprises one or more of a first peptide sequence and one or more of a second peptide sequence, wherein (1) the first peptide sequence is SEQ ID NO:2 or a sequence comprising up to 30% of amino acid of SEQ ID NO:2 deleted or substituted by conservative amino acid substitutions, (2) the second peptide sequence is SEQ ID NO:3 or a sequence comprising up to 30% of amino acid sequence of SEQ ID NO:3 deleted or substituted by conservative amino acid substitutions, and (3) the binding of the polypeptide to antibodies specific for celiac disease and dermatitis herpetiformis is comparable to the binding of the polypeptide according to SEQ ID NO:7 to the antibodies specific for celiac disease and dermatitis herpetiformis. 
     
     
       12. A nucleic acid encoding a polypeptide according to  claim 1 . 
     
     
       13. The method of  claim 8 , wherein the first peptide sequence is SEQ ID NO:2 and the second peptide sequence is SEQ ID NO:3, and wherein SEQ ID NO:2 and SEQ ID NO:3 partially overlap. 
     
     
       14. The method of  claim 8 , wherein the polypeptide comprises one or more polypeptides consisting of at least 10, at least 14, at least 15, or at least 16 successive amino acids of SEQ ID NO:4 or wherein the polypeptide comprises one or more polypeptides according to SEQ ID NO:4. 
     
     
       15. The method according to  claim 8 , comprising three polypeptides according to SEQ ID NO:4. 
     
     
       16. The method according to  claim 8 , comprising one or several polypeptide sequences according to SEQ ID NO:7.